ArticleBrain communications2026
Affective and cognitive theory of mind and associated brain functional alterations in frontotemporal dementia.
Article in Brain communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Theory of mind (ToM), the ability to infer others' beliefs (cognitive ToM) and emotions (affective ToM), is compromised in behavioural variant frontotemporal dementia (bvFTD). However, its diagnostic and prognostic value in other frontotemporal dementia (FTD) variants remains underexplored due to limited understanding of the underlying neural mechanisms. This study investigated whether ToM deficits are shared across the frontotemporal dementia spectrum and explored the functional connectivity alterations underlying these disturbances using resting-state functional magnetic resonance imaging. Sixty-seven FTD patients [14 non-fluent variant primary progressive aphasia (nfvPPA), 17 semantic variant primary progressive aphasia (svPPA), 23 bvFTD, 13 right temporal variant frontotemporal dementia (rtvFTD); 34 women; mean age 66.5 ± 7.7 years] and two control groups (48 age-matched healthy controls; 50 young healthy controls) underwent clinical, neuropsychological and brain magnetic resonance imaging assessments. ToM was evaluated in patients using the Story-Based Empathy Task (SET), which includes the Story-Based Empathy Task affective subtest (SET-EA) and the Story-Based Empathy Task cognitive subtest (SET-IA). Resting-state functional connectivity networks were obtained in young healthy controls using seed-based analysis centred on the left medial prefrontal cortex for affective ToM and the right supramarginal gyrus for cognitive ToM. In addition, four large-scale functional networks were reconstructed to reflect disease-specific vulnerability. Functional brain connectivity within all networks was quantified using graph analysis and connectomics, and between-group comparisons were performed on both global and seed-based regional metrics. All patient groups showed similar impairments in affective and cognitive ToM performance. Network analyses revealed two dissociable but interconnected ToM systems. Global metrics of network topology indicated increased path length and reduced nodal strength in both ToM networks, particularly in bvFTD and nfvPPA patients (
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